A Study of De-immunized DI-Leu16-IL2 Administered Subcutaneously in Participants With B-cell NHL

NCT01874288 | Terminated Phase 1 Results DMC

• 1 other identifier: AO-101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

This dose-escalation study is designed for determining the safety, tolerability, pharmacokinetics (PK), biological, and clinical activity of DI-Leu16-IL2 administered to participants with cluster of differentiation 20 (CD20) positive NHL that have failed standard rituximab-containing therapy.

Conditions

B-cell Non-Hodgkin Lymphoma

Keywords

NHL; Immunocytokine; Lymphoma; Non-Hodgkin; B-cell; IL (interleukin)

Outcome Measures

Primary Outcomes (5)

• Maximum Tolerated Dose (MTD) of DI-Leu16-IL2

  The MTD was determined based on toxicities from the first 2 cycles of treatment. The MTD was the highest dose tested with no more than 1 participant out of 6 experienced a dose-limiting toxicity (DLT). All non-hematologic adverse events (AEs) and all hematologic AEs of greater than Grade 3 were considered relevant to determining DLTs. DLTs included absolute lymphocyte count (ALC) Grade 3 and 4 (if ALC does not resolve to baseline grade according to Common Terminology Criteria for Adverse Events (CTCAE) v4 within 5 days post the final injection per cycle of DI-Leu16-IL2), and absolute neutrophil count (ANC) Grade 3 (If ANC does not resolve to at least Grade 2 within 5 days post the final injection per cycle of DI-Leu16-IL2) and Grade 4 (any).

  First 2 cycles of treatment (each cycle = 21 days)

• Number of Participants With a DLT

  All non-hematologic AEs and all hematologic AEs of greater than Grade 3 were considered relevant to determining DLTs. DLTs included ALC Grade 3 and 4 (if ALC does not resolve to baseline grade according to CTCAE v4 within 5 days post the final injection per cycle of DI-Leu16-IL2), and ANC Grade 3 (If ANC does not resolve to at least Grade 2 within 5 days post the final injection per cycle of DI-Leu16-IL2) and Grade 4 (any).

  First 2 cycles of treatment (each cycle = 21 days)

• Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria

  BOR included complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD). CR: 1) Disappearance of all detectable clinical and radiological evidence of disease; 2) lymph nodes (LN) regressed to normal size; 3) other organs (spleen, liver, kidneys) that were enlarged before therapy must have decreased in size; 4) clear bone marrow (BM) infiltrate. CRu: must meet CR criteria 1 and 3, as well as ≥1 of following: residual LN mass \>1.5 cm in greatest transverse diameter; individual nodes that were previously confluent regressed by \>75% in sum of product diameters (SPD); or indeterminate BM. PR: 6 largest dominant nodes or nodal masses decreased by ≤50% in SPD; no increase in size of other nodes; liver or spleen; splenic and hepatic nodules regressed ≥50% in SPD; and no new disease. SD: less than a PR but not PD. PD: 50% increase from nadir in SPD of any abnormal node for PR or nonresponders and appearance of any new lesion.

  First dose of study drug until first appearance of CR, CRu, PR, SD, or PD (up to 6 months)

• Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study

  Sum of product diameters sums the product of the 2 tumor measurements on each lesion. If only 1 measurement was available, it was used as the longest length and the product of the lengths in the sum. Baseline value is the last non-missing measurement prior to receiving study drug injection. None of the participants were considered evaluable in 'DI-Leu16-IL2 0.5 mg/m\^2' arm for this outcome measure at the end of study, and therefore, data were not collected for that arm.

  Baseline, end of study (EOS) (up to approximately 3 years)

• Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study

  Sum of longest diameters is the sum of the longest measured length of each tumor lesion. Baseline value is the last non-missing measurement prior to receiving study drug injection. None of the participants were considered evaluable in 'DI-Leu16-IL2 0.5 mg/m\^2' arm for this outcome measure at the end of study, and therefore, data were not collected for that arm.

  Baseline, EOS (up to approximately 3 years)

Secondary Outcomes (1)

• Number of Participants With Anti-DI-Leu16-IL2 Antibodies

  First dose of study drug up to EOS (up to approximately 3 years)

Study Arms (5)

DI-Leu16-IL2 0.5 mg/m^2

EXPERIMENTAL

Participants will receive DI-Leu16-IL2 0.5 mg/m\^2 subcutaneously (SC) for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

Drug: DI-Leu16-IL2

DI-Leu16-IL2 1.0 mg/m^2

EXPERIMENTAL

Participants will receive DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

Drug: DI-Leu16-IL2

DI-Leu16-IL2 2.0 mg/m^2

EXPERIMENTAL

Participants will receive DI-Leu16-IL2 2.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

Drug: DI-Leu16-IL2

DI-Leu16-IL2 4.0 mg/m^2

EXPERIMENTAL

Participants will receive DI-Leu16-IL2 4.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles

Drug: DI-Leu16-IL2

DI-Leu16-IL2 6.0 mg/m^2

EXPERIMENTAL

Participants will receive DI-Leu16-IL2 6.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

Drug: DI-Leu16-IL2

Interventions

DI-Leu16-IL2 DRUG

DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.

DI-Leu16-IL2 0.5 mg/m^2; DI-Leu16-IL2 1.0 mg/m^2; DI-Leu16-IL2 2.0 mg/m^2; DI-Leu16-IL2 4.0 mg/m^2; DI-Leu16-IL2 6.0 mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with CD20-expressing B-cell NHL that is relapsed or refractory to standard therapy. Chronic lymphocytic leukemia/small lymphocytic lymphoma with peripheral blood leukemia/lymphoma cells and high-grade lymphomas are excluded.
• Participants must have received prior rituximab-containing therapy.
• Evaluable disease. In the absence of lymphadenopathy, splenomegaly with defects or measurable extra-medullary disease is acceptable.
• Participants who have received a prior autologous stem cell transplant are eligible if the transplant occurred \>6 months ago.
• Participants who have received a prior allogeneic stem cell transplant are eligible if:
• The transplant occurred \>6 months ago
• There is no evidence of active graft versus host disease
• Systemic immunosuppressive agents (including corticosteroids) have not been received for at least 8 weeks
• Karnofsky performance scale ≥70%
• Life expectancy ≥12 weeks
• Adequate baseline functions:
• Serum creatinine ≤1.5 mg/deciliter (dL)
• Total white blood cell (WBC) count ≥3000/microliter (µL) or absolute neutrophil count (ANC) ≥1000/µL
• Absolute lymphocyte count ≥0.75 \* 10\^3/µL
• Platelet count ≥75,000/µL

You may not qualify if:

• Evidence of central nervous system lymphoma or lymphomatous meningitis
• Prior treatment with interleukin 2 (IL2) within the last 5 years
• Type I hypersensitivity or anaphylactic reactions to murine proteins or to previous infusion of rituximab
• Pregnant or lactating female
• An immediate need for palliative radiotherapy or systemic corticosteroid therapy
• Known intercurrent infections (including hepatitis C virus and human immunodeficiency virus or other conditions), or clinical evidence of these conditions
• Actively infected with or chronic carriers of hepatitis B virus as demonstrated by positive hepatitis B core antibody or hepatitis B surface antigen. Participants who are seropositive only, that is, surface antibody positive \[HbsAb\], are permitted.
• Other significant active infection.
• Major surgery, chemotherapy, investigational agent, or radiation within 30 days of Day 1
• Uncontrolled hypertension (diastolic greater to or equal to 100 millimeters of mercury \[mmHg\]) or hypotension (systolic less than or equal to 90 mmHg)
• History of repeated and clinically relevant episodes of syncope or other paroxysmal, ventricular, or other significant arrhythmias
• History of medically significant ascites requiring repetitive paracentesis
• Previous diagnosis of autoimmune disease (Exceptions: participants with autoimmune thyroiditis or vitiligo may be enrolled)
• Organ transplant recipient
• History of prior therapy or a serious, uncontrolled medical disorder that in the Investigator's opinion would impair participation in the study

Sponsors & Collaborators

• Alopexx Oncology, LLC: lead

Study Sites (5)

City of Hope

Duarte, California, 91010, United States

Location

St. Jude Hospital Yorba Linda

Fullerton, California, 92835, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Joe Arlington Cancer Research and Treatment Center

Lubbock, Texas, 97410, United States

Location

Related Publications (3)

• King DM, Albertini MR, Schalch H, Hank JA, Gan J, Surfus J, Mahvi D, Schiller JH, Warner T, Kim K, Eickhoff J, Kendra K, Reisfeld R, Gillies SD, Sondel P. Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. J Clin Oncol. 2004 Nov 15;22(22):4463-73. doi: 10.1200/JCO.2004.11.035. Epub 2004 Oct 13.

  PMID: 15483010 BACKGROUND

• Ko YJ, Bubley GJ, Weber R, Redfern C, Gold DP, Finke L, Kovar A, Dahl T, Gillies SD. Safety, pharmacokinetics, and biological pharmacodynamics of the immunocytokine EMD 273066 (huKS-IL2): results of a phase I trial in patients with prostate cancer. J Immunother. 2004 May-Jun;27(3):232-9. doi: 10.1097/00002371-200405000-00008.

  PMID: 15076141 BACKGROUND

• Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, Levy R. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994 Oct 15;84(8):2457-66.

  PMID: 7522629 BACKGROUND

Related Links

• Sponsor website
• National Cancer Institute at the National Institute of Health

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Clinical benefit was noted in the earlier portion of the trial; hence, participants were not enrolled in 2 expansion cohorts and the study was terminated early.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Alopexx Oncology, LLC

daniel.vlock@alopexx.com

Study Officials

• Daniel Vlock, MD

  Alopexx Oncology, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2013
• First Posted: June 11, 2013
• Study Start: November 25, 2013
• Primary Completion: January 27, 2014
• Study Completion: November 16, 2016
• Last Updated: November 24, 2020
• Results First Posted: November 24, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)